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Relapsed Non-Hodgkin LymphomaPhase 1/2NCT05826535

Study of Rondecabtagene Autoleucel in Aggressive Large B-Cell Lymphoma

A Phase 1/2 study testing Rondecabtagene autoleucel (ronde-cel), Fludarabine and Cyclophosphamide in people with Relapsed Non-Hodgkin Lymphoma and Refractory Non-Hodgkin Lymphoma, run by Lyell Immunopharma, Inc. at 35 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of rondecabtagene autoleucel (ronde-cel) also known as LYL314, a dual-targeting chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive large B-cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Rondecabtagene autoleucel (ronde-cel), Fludarabine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
270 participants
Where
35 sitesin 2 countries
Study dates
9 May 2023to 30 Jun 2031
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 years or older
  • Willing and able to provide written informed consent
  • Histologically confirmed LBCL, including the following types defined by the World Health Organization (WHO 2022) or International Consensus Classification (2022)
  • Received at least two prior lines of therapy for Cohorts 1, 2, and 4 and one prior line of therapy for Cohort 3
  • Relapsed or refractory disease.
  • At least 1 measurable lesion (per Lugano classification)
Show all 11Show fewer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 or ECOG 0 to 2 (Cohort 5)
  • Absolute neutrophil count (ANC) ≥ 1000/µL
  • Platelet count ≥ 50,000/µL
  • Absolute lymphocyte count (ALC) ≥ 200/µL
  • Other protocol-defined criteria apply.

Who cannot join

  • History of malignancy other than non-melanoma skin cancer or carcinoma in situ unless disease-free for at least 3 years
  • Active central nervous system involvement
  • History of cardiac lymphoma involvement or Epstein-Barr virus (EBV)+ lymphoma
  • Ongoing or impending oncologic emergency
  • Recent systemic anti-cancer therapy or radiation
  • Ongoing non-hematologic toxicities due to prior therapy
Show all 12Show fewer
  • History of allogeneic stem cell or solid organ transplantation
  • Autologous stem cell transplantation within 6 weeks
  • History of prior genetically modified cell therapy (Cohorts 1, 3, 4, 5) or no other than a product targeting CD19 with an FMC63-based CAR (e.g., axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or lisocabtagene maraleucel (liso-cel) (Cohort 2).
  • Primary immunodeficiency
  • History of autoimmune disease resulting in end organ injury or requiring recent therapy
  • Other protocol-defined criteria apply.

Trial locations and contacts

35 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Stephen Simko, MD contact

000-000-0000

clinicaltrials@lyell.com

35 sites in 2 countries

United States32 sites, 32 recruiting

  • University of New Mexico Comprehensive Cancer Center

    Albuquerque, New Mexico, 87131

    Recruiting

  • Lehigh Valley Topper Cancer Center Institute

    Allentown, Pennsylvania, 18103

    Recruiting

  • Augusta University Medical Center

    Augusta, Georgia, 30912

    Recruiting

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14263

    Recruiting

  • University of Cincinnati (UC) Physicians Company, LLC

    Cincinnati, Ohio, 45267

    Recruiting

  • Cleveland Clinic

    Cleveland, Ohio, 44195

    Recruiting

  • Baylor University Medical Center

    Dallas, Texas, 75246

    Recruiting

  • Colorado Blood Cancer Institute

    Denver, Colorado, 80218

    Recruiting

  • Corewell Health

    Grand Rapids, Michigan, 49503

    Recruiting

  • John Theurer Cancer Center Hackensack University Medical Center

    Hackensack, New Jersey, 07601

    Recruiting

  • Indiana Blood and Marrow Transplantation

    Indianapolis, Indiana, 46237

    Recruiting

  • University of Iowa

    Iowa City, Iowa, 52242

    Recruiting

  • University of California-Irvine Medical Center

    Irvine, California, 92697

    Recruiting

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

    Recruiting

  • University of California, Los Angeles (UCLA) Medical Center

    Los Angeles, California, 90095

    Recruiting

  • University of Louisville Brown Cancer Center

    Louisville, Kentucky, 40202

    Recruiting

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

    Recruiting

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37212

    Recruiting

  • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

    New York, New York, 10021

    Recruiting

  • Virginia Oncology Associates

    Norfolk, Virginia, 24502

    Recruiting

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

    Recruiting

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

    Recruiting

  • West Penn Hospital

    Pittsburgh, Pennsylvania, 15224

    Recruiting

  • Virginia Commonwealth University-Massey Cancer Center

    Richmond, Virginia, 23298

    Recruiting

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

    Recruiting

  • Intermountain Healthcare

    Salt Lake City, Utah, 84143

    Recruiting

  • Texas Transplant Institute

    San Antonio, Texas, 78229

    Recruiting

  • Scripps Clinic

    San Diego, California, 92037

    Recruiting

  • Louisiana State University Health Sciences Center

    Shreveport, Louisiana, 71130

    Recruiting

  • Montefiore Medical Center

    The Bronx, New York, 10461

    Recruiting

  • Medstar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

    Recruiting

  • Atrium Health Wake Forest Baptist

    Winston-Salem, North Carolina, 27157

    Recruiting

Other trials in United States

Australia3 sites, 3 recruiting

  • The Alfred Hospital

    Melbourne, 3004

    Recruiting

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

    Chan Cheah, MD, (08) 6383 3290, chan.cheah@health.wa.gov.au

    Recruiting

  • Royal Perth Hospital

    Perth, Western Australia, 6000

    Recruiting

Other trials in Australia

About this study

Official title: A Phase 1/2 Multi-Center Study Evaluating the Safety and Efficacy of Rondecabtagene Autoleucel, a CD19/CD20 Dual-Targeting Chimeric Antigen Receptor T-Cell Therapy in Participants With Aggressive B-Cell Non-Hodgkin Lymphoma

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of rondecabtagene autoleucel (ronde-cel) also known as LYL314, a dual-targeting chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive large B-cell lymphoma.

Read the detailed description

This is a Phase 1/2, multi-center, open-label study evaluating the safety and efficacy of ronde-cel, a dual-targeting chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 and CD20 in participants with aggressive large B-cell lymphoma.

Five cohorts of participants will be enrolled:

Cohort 1: (3rd or later line, 3L+) Participants who have received least two prior lines of treatment

Cohort 2: (CAR T-cell experienced, 3L+): Participants who have received at least two prior lines of treatment including one prior CAR T.

Cohort 3: (second line, 2L) Participants with refractory disease or relapse within one year of first-line therapy (second-line).

Cohort 4: (TCE-experienced, 3L+) Participants have received prior T-cell engager therapy and have received at least two prior lines of treatment including one TCE therapy and have not received prior CAR T.

Cohort 5: (high-risk 1st line) Participants receiving first-line treatment who remain with disease on positron emission tomography scanning (PET-positive) after 2 to 3 cycles of standard-of-care chemoimmunotherapy and have not received prior CAR T.

Up to approximately 150 participants (across all cohorts) will be enrolled in the dose finding Phase 1 part of the study.

The Phase 2 pivotal study (PiNACLE) will expand enrollment of Cohort 1 to approximately 120 participants to further evaluate the safety and efficacy of ronde-cel.

Ronde-cel treatment consists of a single administration of CAR transduced autologous T-cells administered intravenously after a conditioning chemotherapy regimen consisting of fludarabine and cyclophosphamide, administered over 3 days.

Individual participants will remain in the active post-treatment follow-up (PTFU) period for approximately 2 years. Participants will continue in long-term follow-up (LTFU) for 15 years from ronde-cel treatment.

Being tested
Rondecabtagene autoleucel (ronde-cel), Fludarabine, Cyclophosphamide
Keywords
CAR T-cell, Non-Hodgkin Lymphoma, CD19/20, CD19, CD20, NHL, Diffuse Large B-cell lymphoma, DLBCL, Transformed follicular lymphoma, TFL, Primary mediastinal B-cell lymphoma, PMBCL, Follicular lymphoma Grade 3B, Large cell follicular lymphoma, Aggressive B-cell NHL, Refractory Aggressive B-Cell Lymphoma, Refractory B-Cell Non-Hodgkin Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, Lymphoma, Large B-Cell, Diffuse
Medical subject headings
Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, B-Cell, Lymphoma, Disease Attributes, Immune System Diseases, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rondecabtagene autoleucel (ronde-cel)Drug

    CAR T-cell therapy

  • FludarabineDrug

    Conditioning chemotherapy

  • CyclophosphamideDrug

    Conditioning chemotherapy

Study groups in NCT05826535
Study groupRoleWhat they receive
Ph1, 3rd or later line, 3L+ have not received prior CAR T (Cohort 1)ExperimentalNot described
Receives: Drug: Rondecabtagene autoleucel (ronde-cel); Drug: Fludarabine; Drug: Cyclophosphamide
Ph1 CAR T experienced, 3L+ received at least two or more prior lines of treatment (Cohort 2)ExperimentalNot described
Receives: Drug: Rondecabtagene autoleucel (ronde-cel); Drug: Fludarabine; Drug: Cyclophosphamide
Ph1, 2L Refractory/relapse within 1 year of 1st-line therapy & no prior CAR T (Cohort 3)ExperimentalNot described
Receives: Drug: Rondecabtagene autoleucel (ronde-cel); Drug: Fludarabine; Drug: Cyclophosphamide
Ph1 (T-cell engager experienced, 3L+) received at least 2 prior lines including 1 TCE (Cohort 4)ExperimentalNot described
Receives: Drug: Rondecabtagene autoleucel (ronde-cel); Drug: Fludarabine; Drug: Cyclophosphamide
Ph1 high risk 1st line, PET-positive after 2-3 cycles chemoimmunotherapy, no prior CAR T (Cohort 5)ExperimentalNot described
Receives: Drug: Rondecabtagene autoleucel (ronde-cel); Drug: Fludarabine; Drug: Cyclophosphamide
Ph2, 3rd or later line, have not received prior CAR T (Cohort 1)ExperimentalSingle dose determined during Phase 1.
Receives: Drug: Rondecabtagene autoleucel (ronde-cel); Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent

    Incidence of dose-limiting toxicities (DLTs) and other treatment-emergent adverse events (TEAEs)

    Measured: Baseline to Month 24

  2. Phase 2: Estimate the efficacy of ronde-cel, as measured by overall response rate (ORR)

    ORR based on Independent Review Committee (IRC) assessment per Lugano criteria

    Measured: Baseline to Month 24

Secondary outcomes (10)

  1. Phase 1: Evaluate the efficacy of ronde-cel

    Overall response rate (ORR), Complete response rate (CRR), duration of response (DOR), duration of complete response (DOCR), progression free survival (PFS) based on Investigator assessment until a pivotal trial (Phase 2) portion is initiated at which time all scans will be reviewed by an IRC assessment (Cohort 1) per Lugano criteria

    Measured: Baseline to Month 24

  2. Phase 1: Evaluate the feasibility of treatment with ronde-cel

    Proportion of enrolled participants who receive the target dose of ronde-cel

    Measured: Baseline to Month 24

  3. Phase 1: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent

    Maximum concentration (Cmax), area under the curve from time 0 to Day 28 (AUC0-28) and persistence of ronde-cel

    Measured: Baseline to Month 24

  4. Phase 2: Estimate the efficacy of ronde-cel

    ORR based on Investigator assessment per Lugano criteria

    Measured: Baseline to Month 24

  5. Phase 2: Estimate the efficacy of ronde-cel

    DOR based on IRC assessment and investigator assessment per Lugano criteria

    Measured: Baseline to Month 24

  6. Phase 2: Estimate the efficacy of ronde-cel

    Time to response (TTR) based on IRC assessment and investigator assessment per Lugano criteria

    Measured: Baseline to Month 24

  7. Phase 2: Estimate the efficacy of ronde-cel

    PFS based on IRC assessment and investigator assessment per Lugano criteria

    Measured: Baseline to Month 24

  8. Phase 2: Estimate the efficacy of ronde-cel

    Overall Survival (OS)

    Measured: Baseline to Month 72

  9. Phase 2: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent

    Incidence and severity of TEAEs

    Measured: Baseline to Month 24

  10. Phase 2: Evaluate the pharmacokinetics of ronde-cel when administered as a single agent

    Maximum concentration (Cmax), area under the curve from time 0 to Day 28 (AUC0-28) and persistence of ronde-cel

    Measured: Baseline to Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2023
  2. Study start9 May 2023
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion30 Jun 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
270 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05826535
Sponsor's protocol ID
LYL314-101
Status last verified
Apr 2026
First submitted
24 Mar 2023
Last updated
25 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Rondecabtagene autoleucel (ronde-cel), Fludarabine and Cyclophosphamide in people with Relapsed Non-Hodgkin Lymphoma and Refractory Non-Hodgkin Lymphoma, run by Lyell Immunopharma, Inc. at 35 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 35 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Stephen Simko, MD (000-000-0000, clinicaltrials@lyell.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Evaluate the safety and tolerability of a single dose of ronde-cel administered as a single agent (time frame: Baseline to Month 24). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05826535.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2026.

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